Background

By the time C. difficile patients get to Johan S. Bakken, MD, FACP, an infectious disease specialist and clinical
associate professor at the University of Minnesota, they have already tried almost
everything.

“Most of the patients referred to me have been given customary probiotic agents,”
said Dr. Bakken. They have also tried the usual antibiotics, metronidazole or vancomycin.
Traditionally, after those treatments fail and the patients suffer with diarrhea,
for years in some cases, they come to Dr. Bakken for the last resort—fecal
microbiota transplantation.

But transplantation isn't possible for some patients. “For various reasons,
[patients] elect not to pursue that form of treatment, either because they can't afford
it, that is, the cost of screening the donor of the fecal sample; or they have adverse
opinions about fecal transplantation; or they simply can't locate a donor of stool,”
said Dr. Bakken.

How it works

This led him to contemplate alternative treatments for recurrent C. difficile. “It dawned on me why all these treatments had failed had to do with the fact
that none of the programs dealt with the spores that were left in the colon,”
said Dr. Bakken. “When [C. difficile] convert to a spore-form stage, then the antibiotic agents have no impact on their
survival. It seemed that one would need to think along the lines of a bacterium.”

To trick the bacteria, Dr. Bakken came up with a staggered, tapered antibiotic withdrawal
regimen. Once a patient was diarrhea-free on a typical anti-C. diff antibiotic regimen, the doses would be stretched to 72-hour intervals with a reduction
in dose every 2 weeks, for a total of 6 weeks. “My theory was that over time,
you would basically deplete the spore reservoirs so that there would be very, very
few actively growing C. diff organisms in the colon,” Dr. Bakken said.

To further confound the organisms, his patients drank kefir, a fermented milk product
containing 10 to 12 probiotic agents, with every meal. “The probiotic agents
may occupy binding sites that C. diff also needs to occupy and they may compete for food sources. They may have positive
beneficial interactions in the immune system on the epithelial lining, in the intestinal
tract. They may even promote substances that are injurious or noxious to C. diff,” he said.

Results

From 2009 to 2012, Dr. Bakken tried the regimen on 8 patients, all of whom were cured.
Based on that success, he treated 18 more. “I kind of made it into a habit
of offering either fecal transplantation or the taper program,” he said.

One patient didn't comply and dropped out. Of the other 17, all but 4 were diarrhea-free
at 9 months. Those 4 were successfully treated with 2 weeks of vancomycin followed
by 2 weeks of rifaximin. The results suggest that the combination of the antibiotic
withdrawal and the kefir could be as effective a treatment for recurrent C. difficile as fecal transplant, Dr. Bakken concluded when he published his results in the June
27 Clinical Infectious Diseases.

The cost of the regimen—kefir drinks and about 100 vancomycin tablets—is
likely less than the screening and procedure expenses of fecal transplantation, and
the risk of adverse effects appears to be low, according to Dr. Bakken. “The
biggest risk is that it doesn't work. I'm not aware of any risks with the intake of
kefir . . . It's an over-the-counter agent that can be purchased virtually everywhere,”
he said.

Challenges

“Ideally, we should have a randomized protocol, a prospective clinical trial,
that compares this type of treatment to standard treatment, a gradual taper, or perhaps
even fecal transplantation,” said Dr. Bakken.

However, such a trial would require significant funding, so the evidence is likely
to remain anecdotal for a while. “I've discussed this treatment approach with
colleagues who also adopted this, and the feedback I've gotten has been that it has
worked. I don't know how many patients have been subjected to this treatment, but
I haven't had any feedback that says that this doesn't work,” said Dr. Bakken.

Next steps

Dr. Bakken hopes to get more feedback if the publication of his treatment regimen
encourages other clinicians to test it out. Patients, at least, appear to be ready.
“I've received correspondence from potential patients that have gone online
and found [my study],” he said. “I hope this provides an alternative
to a very difficult and prevalent problem.”

ACP Hospitalist provides news and information for hospitalists, covering the major issues in the field. All published material, which is covered by copyright, represents the views of the contributor and does not reflect the opinion of the American College of Physicians or any other institution unless clearly stated.